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High basal level gene expression of thymidine phosphorylase (platelet-derived endothelial cell growth factor) in colorectal tumors is associated with nonresponse to 5-fluorouracil
The gene expression levels of the nucleoside cleavage enzyme/angiogenic factor thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, were measured by quantitative reverse transcription-PCR in 38 pretreatment biopsies of colorectal tumors from patients who were...
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Published in: | Clinical cancer research 1998-10, Vol.4 (10), p.2371-2376 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | The gene expression levels of the nucleoside cleavage enzyme/angiogenic factor thymidine phosphorylase (TP), also known as
platelet-derived endothelial cell growth factor, were measured by quantitative reverse transcription-PCR in 38 pretreatment
biopsies of colorectal tumors from patients who were subsequently treated with 5-fluorouracil (5-FUra) and leucovorin (LV).
The range of TP gene expression (relative mRNA levels) in those tumors nonresponsive to 5-FUra was much broader than that
of the responding tumors. In contrast to in vitro studies that had shown that an increased intracellular level of TP potentiates
the activity of 5-FUra by converting it to the more cytotoxic nucleoside form 5-fluoro-2'deoxyuridine, tumors with the highest
basal TP expressions were nonresponders to 5-FUra/LV therapy. The mean TP mRNA level in the nonresponding tumors was 2.6-fold
higher than that of the responding patients. We had shown previously that high expression of thymidylate synthase (TS), the
target enzyme of 5-FUra, was also a predictor of nonresponse to 5-FUra (L. Leichman et al, J. Clin. Oncol., 15: 3223-3229,
1997). TP and TS expressions were found to be independent variables in these tumors, so that low expression levels of both
TS and TP in tumors predicted a very high response rate (11 of 14) to 5-FUra/LV as well as a significantly longer survival,
whereas none (0 of 24) of the patients with high expression of either TP or TS were responders. |
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ISSN: | 1078-0432 1557-3265 |